MCID: EST007
MIFTS: 37

Estrogen Resistance

Categories: Genetic diseases, Reproductive diseases, Endocrine diseases, Rare diseases

Aliases & Classifications for Estrogen Resistance

MalaCards integrated aliases for Estrogen Resistance:

Name: Estrogen Resistance 57 75 29 13 6 40 73
Estrogen Resistance Syndrome 59 37
Estrogen Insensitivity 57 75
Estrr 57 75

Characteristics:

Orphanet epidemiological data:

59
estrogen resistance syndrome
Inheritance: Autosomal recessive;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
based on 2 reported patients, 1 male and 1 female (last curated august 2013)


HPO:

32
estrogen resistance:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Estrogen Resistance

UniProtKB/Swiss-Prot : 75 Estrogen resistance: A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present.

MalaCards based summary : Estrogen Resistance, also known as estrogen resistance syndrome, is related to aromatase deficiency and breast cancer. An important gene associated with Estrogen Resistance is ESR1 (Estrogen Receptor 1), and among its related pathways/superpathways are Endocrine resistance and Prolactin signaling pathway. Affiliated tissues include bone, breast and uterus, and related phenotypes are hypoplasia of the uterus and primary amenorrhea

Wikipedia : 76 Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen... more...

Description from OMIM: 615363

Related Diseases for Estrogen Resistance

Diseases related to Estrogen Resistance via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 aromatase deficiency 11.3
2 breast cancer 10.1
3 colorectal cancer 9.5
4 leukemia 9.5
5 lymphoma 9.5
6 esophagitis 9.5
7 adenocarcinoma 9.5
8 endotheliitis 9.5
9 endometriosis of ovary 9.4 ESR1 TRERF1

Graphical network of the top 20 diseases related to Estrogen Resistance:



Diseases related to Estrogen Resistance

Symptoms & Phenotypes for Estrogen Resistance

Symptoms via clinical synopsis from OMIM:

57
Skeletal:
osteopenia
delayed bone age (in male and female patients)
low trabecular volumetric bone density (in male patient)
low cortical volumetric bone density (in male patient)

Growth Height:
continued growth into adulthood (in male and female patients)

Chest Breasts:
absent breast development
breast development unresponsive to oral estrogen

Skeletal Spine:
decreased bone mineral density of lumbar spine (in male patient)

Skin Nails Hair Skin:
acanthosis nigricans, axillary (in male patient)
severe facial acne (in female patient)

Genitourinary Internal Genitalia Female:
primary amenorrhea
small uterus
large multicystic ovaries

Cardiovascular Heart:
early atherosclerosis of coronary artery (in male patient)

Genitourinary External Genitalia Female:
tanner stage 4 pubic hair

Skeletal Limbs:
incomplete epiphyseal closures in adulthood (in male and female patients)

Endocrine Features:
elevated serum estradiol (in male and female patients)
elevated serum estrone (in male and female patients)
elevated serum follicle-stimulating hormone (in male and female patients)
elevated serum luteinizing hormone (in male and female patients)
hyperinsulinemia (in male patient)
more

Clinical features from OMIM:

615363

Human phenotypes related to Estrogen Resistance:

59 32 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypoplasia of the uterus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000013
2 primary amenorrhea 59 32 hallmark (90%) Very frequent (99-80%) HP:0000786
3 increased circulating gonadotropin level 59 32 hallmark (90%) Very frequent (99-80%) HP:0000837
4 osteopenia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000938
5 osteoporosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000939
6 overgrowth 59 32 hallmark (90%) Very frequent (99-80%) HP:0001548
7 delayed epiphyseal ossification 59 32 hallmark (90%) Very frequent (99-80%) HP:0002663
8 breast hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0003187
9 marked delay in bone age 59 32 hallmark (90%) Very frequent (99-80%) HP:0003799
10 absence of secondary sex characteristics 59 32 hallmark (90%) Very frequent (99-80%) HP:0008187
11 absence of pubertal development 59 32 hallmark (90%) Very frequent (99-80%) HP:0008197
12 enlarged polycystic ovaries 59 32 hallmark (90%) Very frequent (99-80%) HP:0008675
13 glucose intolerance 59 32 frequent (33%) Frequent (79-30%) HP:0000833
14 hyperinsulinemia 59 32 frequent (33%) Frequent (79-30%) HP:0000842
15 acanthosis nigricans 59 32 frequent (33%) Frequent (79-30%) HP:0000956
16 acne 59 32 frequent (33%) Frequent (79-30%) HP:0001061
17 episodic abdominal pain 59 32 frequent (33%) Frequent (79-30%) HP:0002574
18 elevated tissue non-specific alkaline phosphatase 59 32 frequent (33%) Frequent (79-30%) HP:0010679
19 tall stature 59 Very frequent (99-80%)
20 abnormality of circulating hormone level 59 Very frequent (99-80%)
21 coronary atherosclerosis 59 Frequent (79-30%)
22 abnormality of the adrenal glands 59 Excluded (0%)
23 abnormal testosterone level 59 Excluded (0%)
24 abnormality of the pubic hair 59 Excluded (0%)
25 delayed skeletal maturation 32 HP:0002750
26 coronary artery atherosclerosis 32 frequent (33%) HP:0001677

GenomeRNAi Phenotypes related to Estrogen Resistance according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 9.02 BCAR1 BCAR3
2 Decreased viability GR00381-A-1 9.02 BCAR3
3 Decreased viability GR00402-S-2 9.02 BCAR1 BCAR3

Drugs & Therapeutics for Estrogen Resistance

Search Clinical Trials , NIH Clinical Center for Estrogen Resistance

Genetic Tests for Estrogen Resistance

Genetic tests related to Estrogen Resistance:

# Genetic test Affiliating Genes
1 Estrogen Resistance 29 ESR1

Anatomical Context for Estrogen Resistance

MalaCards organs/tissues related to Estrogen Resistance:

41
Bone, Breast, Uterus, Ovary, Adrenal Gland, Endothelial, B Cells

Publications for Estrogen Resistance

Articles related to Estrogen Resistance:

(show all 30)
# Title Authors Year
1
TGF-I^ Stimulation of EMT Programs Elicits Non-genomic ER-I+ Activity and Anti-estrogen Resistance in Breast Cancer Cells. ( 28955730 )
2017
2
Human enhancer of filamentation 1-induced colorectal cancer cell migration: Role of serine phosphorylation and interaction with the breast cancer anti-estrogen resistance 3 protein. ( 25817040 )
2015
3
A new class of small molecule estrogen receptor-alpha antagonists that overcome anti-estrogen resistance. ( 26575173 )
2015
4
Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) Drives Proliferation of IPH-926 lobular Carcinoma Cells. ( 26317614 )
2015
5
Stromal cells promote anti-estrogen resistance of breast cancer cells through an insulin-like growth factor binding protein 5 (IGFBP5)/B-cell leukemia/lymphoma 3 (Bcl-3) axis. ( 26515727 )
2015
6
Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity. ( 26387946 )
2015
7
Breast cancer anti-estrogen resistance 3 inhibits transforming growth factor I^/Smad signaling and associates with favorable breast cancer disease outcomes. ( 25499443 )
2014
8
Expression of breast cancer anti-estrogen resistance 1 in relation to vascular endothelial growth factor, p53, and prognosis in esophageal squamous cell cancer. ( 22816673 )
2013
9
Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant. ( 23841731 )
2013
10
Reproductive endocrinology: ESR1 mutation causes estrogen resistance and puberty delay in women. ( 23897169 )
2013
11
Breast-cancer anti-estrogen resistance 4 (BCAR4) encodes a novel maternal-effect protein in bovine and is expressed in the oocyte of humans and other non-rodent mammals. ( 23202989 )
2013
12
Paradoxical roles for FOXA1 in anti-estrogen resistance and as a luminal differentiation factor in breast cancer. ( 25083421 )
2012
13
Breast cancer anti-estrogen resistance 3 (BCAR3) protein augments binding of the c-Src SH3 domain to Crk-associated substrate (p130cas). ( 22711540 )
2012
14
Breast cancer anti-estrogen resistance protein 1 (BCAR1/p130cas) in pulmonary disease tissue and serum. ( 21469768 )
2011
15
Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells. ( 22041887 )
2011
16
The substrate domain of BCAR1 is essential for anti-estrogen-resistant proliferation of human breast cancer cells. ( 19412734 )
2010
17
Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. ( 21170268 )
2010
18
Selective recruitment of breast cancer anti-estrogen resistance genes and relevance for breast cancer progression and tamoxifen therapy response. ( 19966015 )
2010
19
AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology. ( 17427198 )
2007
20
AND-34 activates phosphatidylinositol 3-kinase and induces anti-estrogen resistance in a SH2 and GDP exchange factor-like domain-dependent manner. ( 15671247 )
2005
21
Creation of estrogen resistance in vivo by transgenic overexpression of the heterogeneous nuclear ribonucleoprotein-related estrogen response element binding protein. ( 15976060 )
2005
22
[Estrogen resistance and aromatase deficiency in humans]. ( 12462077 )
2002
23
Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. ( 11139588 )
2001
24
Increased expression of cytochrome p450 1A1 and 1B1 genes in anti-estrogen-resistant human breast cancer cell lines. ( 11093812 )
2000
25
BCAR1, a human homologue of the adapter protein p130Cas, induces anti-estrogen resistance in breast cancer cells. ( 10639512 )
2000
26
Aromatase deficiency and estrogen resistance: from molecular genetics to clinic. ( 11305285 )
2000
27
Reversal of estrogen-resistance in murine mammary adenocarcinomas. ( 10424399 )
1999
28
Identification of a novel breast-cancer-anti-estrogen-resistance (BCAR2) locus by cell-fusion-mediated gene transfer in human breast-cancer cells. ( 9259413 )
1997
29
Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. ( 8090165 )
1994
30
R-verapamil decreases anti-estrogen resistance in a breast cancer model. ( 1676580 )
1991

Variations for Estrogen Resistance

UniProtKB/Swiss-Prot genetic disease variations for Estrogen Resistance:

75
# Symbol AA change Variation ID SNP ID
1 ESR1 p.Gln375His VAR_070072 rs397509428
2 ESR1 p.Arg394His VAR_078516

ClinVar genetic disease variations for Estrogen Resistance:

6
(show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 ESR1 NM_001122742.1(ESR1): c.469C> T (p.Arg157Ter) single nucleotide variant Pathogenic rs104893956 GRCh37 Chromosome 6, 152163748: 152163748
2 ESR1 NM_001122742.1(ESR1): c.469C> T (p.Arg157Ter) single nucleotide variant Pathogenic rs104893956 GRCh38 Chromosome 6, 151842613: 151842613
3 ESR1 NM_000125.3(ESR1): c.1125G> T (p.Gln375His) single nucleotide variant Pathogenic rs397509428 GRCh37 Chromosome 6, 152332819: 152332819
4 ESR1 NM_000125.3(ESR1): c.1125G> T (p.Gln375His) single nucleotide variant Pathogenic rs397509428 GRCh38 Chromosome 6, 152011684: 152011684
5 CCDC170; ESR1 NM_025059.3(CCDC170): c.1710+1144T> G single nucleotide variant Uncertain significance rs12662670 GRCh37 Chromosome 6, 151918856: 151918856
6 CCDC170; ESR1 NM_025059.3(CCDC170): c.1710+1144T> G single nucleotide variant Uncertain significance rs12662670 GRCh38 Chromosome 6, 151597721: 151597721
7 CCDC170 NM_025059.3(CCDC170): c.1810G> A (p.Val604Ile) single nucleotide variant Likely pathogenic rs6929137 GRCh37 Chromosome 6, 151936677: 151936677
8 CCDC170 NM_025059.3(CCDC170): c.1810G> A (p.Val604Ile) single nucleotide variant Likely pathogenic rs6929137 GRCh38 Chromosome 6, 151615542: 151615542
9 CCDC170 NM_025059.3(CCDC170): c.*68A> C single nucleotide variant Uncertain significance rs3734805 GRCh37 Chromosome 6, 151939350: 151939350
10 CCDC170 NM_025059.3(CCDC170): c.*68A> C single nucleotide variant Uncertain significance rs3734805 GRCh38 Chromosome 6, 151618215: 151618215
11 CCDC170 NM_025059.3(CCDC170): c.*978A> G single nucleotide variant Uncertain significance rs9383589 GRCh37 Chromosome 6, 151940260: 151940260
12 CCDC170 NM_025059.3(CCDC170): c.*978A> G single nucleotide variant Uncertain significance rs9383589 GRCh38 Chromosome 6, 151619125: 151619125
13 CCDC170 NC_000006.12: g.151625494T> A single nucleotide variant Uncertain significance rs12665607 GRCh37 Chromosome 6, 151946629: 151946629
14 CCDC170 NC_000006.12: g.151625494T> A single nucleotide variant Uncertain significance rs12665607 GRCh38 Chromosome 6, 151625494: 151625494
15 CCDC170 NC_000006.12: g.151627231G> A single nucleotide variant Likely pathogenic rs2046210 GRCh37 Chromosome 6, 151948366: 151948366
16 CCDC170 NC_000006.12: g.151627231G> A single nucleotide variant Likely pathogenic rs2046210 GRCh38 Chromosome 6, 151627231: 151627231
17 CCDC170 NC_000006.12: g.151630085A> G single nucleotide variant Uncertain significance rs9397435 GRCh37 Chromosome 6, 151951220: 151951220
18 CCDC170 NC_000006.12: g.151630085A> G single nucleotide variant Uncertain significance rs9397435 GRCh38 Chromosome 6, 151630085: 151630085
19 ESR1 NM_000125.3(ESR1): c.1181G> A (p.Arg394His) single nucleotide variant Likely pathogenic rs1131692059 GRCh37 Chromosome 6, 152332875: 152332875
20 ESR1 NM_000125.3(ESR1): c.1181G> A (p.Arg394His) single nucleotide variant Likely pathogenic rs1131692059 GRCh38 Chromosome 6, 152011740: 152011740

Expression for Estrogen Resistance

Search GEO for disease gene expression data for Estrogen Resistance.

Pathways for Estrogen Resistance

Pathways related to Estrogen Resistance according to KEGG:

37
# Name Kegg Source Accession
1 Endocrine resistance hsa01522
2 Prolactin signaling pathway hsa04917
3 Estrogen signaling pathway hsa04915

Pathways related to Estrogen Resistance according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.13 BCAR1 BCAR3
2 10.04 BCAR1 ESR1

GO Terms for Estrogen Resistance

Sources for Estrogen Resistance

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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